Dysfunctions in mitochondria – the powerhouses of the cell – lead to several human pathologies. Because mitochondria integrate nuclear and mitochondrial genetic systems, they are richly intertwined with cellular activities. The nucleus-encoded mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are key components of the mitochondrial translation apparatus. Mutations in these enzymes predominantly affect the central nervous system (CNS) but also target other organs. Comparable mutations in mt-aaRSs can lead to vastly diverse diseases, occurring at different stages in life, and within different tissues; this represents a confounding issue. With newer information available, we propose that the pleiotropy and tissue-specificity of mt-aaRS-associated diseases result from the molecular integration of mitochondrial translation events within the cell; namely, through specific crosstalk between the cellular program and the energy demands of the cell. We place particular focus on neuronal cells.

线粒体功能失调-细胞的强大力量-导致多种人类疾病。由于线粒体整合了核和线粒体遗传系统，因此它们与细胞活动紧密地交织在一起。核编码的线粒体氨酰基-tRNA合成酶（mt-aaRSs）是线粒体翻译设备的关键组成部分。这些酶的突变主要影响中枢神经系统（CNS），但也靶向其他器官。mt-aaRSs中可比的突变会导致多种多样的疾病，发生在生命的不同阶段和不同组织内。这代表了一个令人困惑的问题。利用最新的信息，我们提出mt-aaRS相关疾病的多效性和组织特异性是由细胞内线粒体翻译事件的分子整合引起的。即，通过蜂窝程序与单元的能量需求之间的特定串扰。我们特别关注神经元细胞。